High ethanol preference and dissociated memory are co-occurring phenotypes associated with hippocampal GABAAR-δ receptor levels.

Alcohol use disorder (AUD) frequently co-occurs with dissociative disorders and disorders with dissociative symptoms, suggesting a common neurobiological basis. It has been proposed that facilitated information processing under the influence of alcohol, resulting in the formation of dissociated memories, might be an important factor controlling alcohol use. Access to such memories is facilitated under the effect of alcohol, thus further reinforcing alcohol use. To interrogate possible mechanisms associated with these phenotypes, we used a mouse model of dissociative amnesia, combined with a high-alcohol preferring (HAP) model of AUD. Dissociated memory was induced by activation of hippocampal extrasynaptic GABA type A receptor delta subunits (GABAAR-δ), which control tonic inhibition and to which ethanol binds with high affinity. Increased ethanol preference was associated with increased propensity to form dissociated memories dependent on GABAAR-δ in the dorsal hippocampus (DH). Furthermore, the DH level of GABAAR-δ protein, but not mRNA, was increased in HAP mice, and was inversely correlated to the level of miR-365-3p, suggesting an miRNA-mediated post-transcriptional mechanism contributing to elevated GABAAR-δ. The observed changes of DH GABAAR-δ were associated with a severe reduction of excitatory projections stemming from GABAAR-δ-containing pyramidal neurons in the subiculum and terminating in the mammillary body. These results suggest that both molecular and circuit dysfunction involving hippocampal GABAAR-δ receptors might contribute to the co-occurrence of ethanol preference and dissociated information processing.

Mammillary body atrophy and other MRI correlates of school-age outcome following neonatal hypoxic-ischemic encephalopathy.

The mammillary bodies (MB) and hippocampi are important for memory function and are often affected following neonatal hypoxic ischemic encephalopathy (HIE). The aim of this study was to assess neurodevelopmental outcome in 10-year-old children with HIE with and without therapeutic hypothermia. Additional aims were to assess the associations between MB atrophy, brain volumes (including the hippocampi), white matter microstructure and neurodevelopmental outcome at school-age. Ten-year-old children with HIE were included, who were treated with therapeutic hypothermia (n = 22) or would have qualified but were born before this became standard of care (n = 28). Children completed a neuropsychological and motor assessment and MRI. Mammillary bodies were scored as normal or atrophic at 10 years. Brain volumes were segmented on childhood MRI and DTI scans were analysed using tract-based spatial statistics. Children with HIE suffered from neurocognitive and memory problems at school-age, irrespective of hypothermia. Hippocampal volumes and MB atrophy were associated with total and performance IQ, processing speed and episodic memory in both groups. Normal MB and larger hippocampi were positively associated with global fractional anisotropy. In conclusion, injury to the MB and hippocampi was associated with neurocognition and memory at school-age in HIE and might be an early biomarker for neurocognitive and memory problems.

Reduced brain mammillary body volumes and memory deficits in adolescents who have undergone the Fontan procedure.

BACKGROUND: Adolescents with single ventricle heart disease (SVHD) who have undergone the Fontan procedure show cognitive/memory deficits. Mammillary bodies are key brain sites that regulate memory; however, their integrity in SVHD is unclear. We evaluated mammillary body (MB) volumes and their associations with cognitive/memory scores in SVHD and controls. METHODS: Brain MRI data were collected from 63 adolescents (25 SVHD; 38 controls) using a 3.0-Tesla MRI scanner. Cognition and memory were assessed using Montreal Cognitive Assessment (MoCA) and Wide Range Assessment of Memory and Learning 2. MB volumes were calculated and compared between groups (ANCOVA, covariates: age, sex, and total brain volume [TBV]). Partial correlations and linear regression were performed to examine associations between volumes and cognitive scores (covariates: age, sex, and TBV). RESULTS: SVHD group showed significantly lower MoCA and WRAML2 scores over controls. MB volumes were significantly reduced in SVHD over controls. After controlling for age, sex, and TBV, MB volumes correlated with MoCA and delayed memory recall scores in SVHD and controls. CONCLUSION: Adolescents with SVHD show reduced MB volumes associated with cognitive/memory deficits. Potential mechanisms of volume losses may include developmental and/or hypoxic/ischemic-induced processes. Providers should screen for cognitive deficits and explore possible interventions to improve memory.

Lesions of the head direction cell system impair direction discrimination.

Previous results suggest that directional information from the head direction cell circuit may inform hippocampal place cell firing when an animal is confronted with visually identical environments. To investigate whether such information might also be essential for spatial behavior, we tested adult, male Lister Hooded rats that had received either bilateral lateral mammillary nuclei (LMN) lesions or sham lesions on a four-way, conditional odor-location discrimination in compartments arranged at 60° to one another. We found that significantly fewer rats in the LMN lesion group were able to learn the task compared to the Sham group. We also found that the extent of the behavioral impairment was highly correlated with the degree of tissue loss in the LMN resulting from the lesion. Animals with LMN lesions were also impaired in a nonmatching-to-sample task in a T maze, and the extent of impairment likewise depended on the extent of the lesion. Performance in the odor-location and T-maze tasks was not affected by tissue loss in the medial mammillary nuclei. Together, these results indicate that the LMN, a key node in the head direction circuit, is critical for solving a spatial task that requires a directional discrimination. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Mammillothalamic Disconnection Alters Hippocampocortical Oscillatory Activity and Microstructure: Implications for Diencephalic Amnesia.

Diencephalic amnesia can be as debilitating as the more commonly known temporal lobe amnesia, yet the precise contribution of diencephalic structures to memory processes remains elusive. Across four cohorts of male rats, we used discrete lesions of the mammillothalamic tract to model aspects of diencephalic amnesia and assessed the impact of these lesions on multiple measures of activity and plasticity within the hippocampus and retrosplenial cortex. Lesions of the mammillothalamic tract had widespread indirect effects on hippocampocortical oscillatory activity within both theta and gamma bands. Both within-region oscillatory activity and cross-regional synchrony were altered. The network changes were state-dependent, displaying different profiles during locomotion and paradoxical sleep. Consistent with the associations between oscillatory activity and plasticity, complementary analyses using several convergent approaches revealed microstructural changes, which appeared to reflect a suppression of learning-induced plasticity in lesioned animals. Together, these combined findings suggest a mechanism by which damage to the medial diencephalon can impact upon learning and memory processes, highlighting an important role for the mammillary bodies in the coordination of hippocampocortical activity.SIGNIFICANCE STATEMENT Information flow within the Papez circuit is critical to memory. Damage to ascending mammillothalamic projections has consistently been linked to amnesia in humans and spatial memory deficits in animal models. Here we report on the changes in hippocampocortical oscillatory dynamics that result from chronic lesions of the mammillothalamic tract and demonstrate, for the first time, that the mammillary bodies, independently of the supramammillary region, contribute to frequency modulation of hippocampocortical theta oscillations. Consistent with the associations between oscillatory activity and plasticity, the lesions also result in a suppression of learning-induced plasticity. Together, these data support new functional models whereby mammillary bodies are important for coordinating hippocampocortical activity rather than simply being a relay of hippocampal information as previously assumed.

Mammillary body changes and seizure outcome after laser interstitial thermal therapy of the mesial temporal lobe.

OBJECTIVE: The mammillary bodies have long been known as the primary relay center for the hippocampus. The fornix is the primary efferent pathway of the hippocampus, with its postcommissural fibers terminating in the mammillary bodies. In this study, we describe change in mammillary body volume after laser interstitial thermal therapy (LiTT) for mesial temporal lobe epilepsy and correlate it with seizure outcome. METHODS: Pre- and post-LiTT ablation magnetic resonance imaging was reviewed in axial and coronal planes to determine mammillary body volume as calculated by the ellipsoid method. Patient demographics, clinical semiology, and seizure localization were analyzed. The primary end-point was seizure freedom at 1 year after LiTT. The change in the size of the mammillary body were correlated with the postoperative seizure freedom at 1 year using the Wilcoxon/Kruskal-Wallis test for statistical significance. RESULTS: Between December 1, 2012 and June 1, 2015, 22 patients underwent LiTT for mesial temporal lobe epilepsy. Two patients were excluded due to lack of follow-up. Of the remaining 20 patients, 13 were seizure free at 1 year. In the seizure free group, there was an average 34.6% (±â€¯13%) decline in ipsilateral mammillary body volume, as opposed to an average decline of 8.4% (±â€¯10.9%) in patients with continued seizures (P = 0.0026). CONCLUSIONS: Our findings show a statistically significant correlation between postoperative volume reduction in ipsilateral mammillary body and seizure outcomes after LiTT. With further validation, this finding could be a useful marker of adequacy of ablation independent of ablation volumes and determinant of potential benefit of additional surgical intervention in patients with poor outcomes after LiTT.

Lesions within the head direction system reduce retrosplenial c-fos expression but do not impair performance on a radial-arm maze task.

The lateral mammillary nuclei are a central structure within the head direction system yet there is still relatively little known about how these nuclei contribute to spatial performance. In the present study, rats with selective neurotoxic lesions of the lateral mammillary nuclei were tested on a working memory task in a radial-arm maze. This task requires animals to distinguish between eight radially-oriented arms and remember which arms they have entered within a session. Even though it might have been predicted that this task would heavily tax the head direction system, the lesion rats performed equivalently to their surgical controls on this task; no deficit emerged even when the task was made more difficult by rotating the maze mid-way through testing in order to reduce reliance on intramaze cues. Rats were subsequently tested in the dark to increase the use of internally generated direction cues but the lesion rats remained unimpaired. In contrast, the lateral mammillary nuclei lesions were found to decrease retrosplenial c-Fos levels. These results would suggest that the head direction system is not required for the acquisition of the standard radial-arm maze task. It would also suggest that small decreases in retrosplenial c-Fos are not sufficient to produce behavioural impairments.

Long-term effects of sleep deprivation on neuronal activity in four hypothalamic areas.

Lack of adequate sleep has become increasingly common in our 24/7 society. Unfortunately diminished sleep has significant health consequences including metabolic and cardiovascular disease and mental disorders including depression. The pathways by which reduced sleep adversely affects physiology and behavior are unknown. We found that 6h of sleep deprivation in adult male rats induces changes in neuronal activity in the lateral hypothalamus, the paraventricular nucleus, the arcuate nucleus and the mammillary bodies. Surprisingly, these alterations last for up to 48h. The data show that sleep loss has prolonged effects on the activity of multiple hypothalamic areas. Our data indicate also that measuring electroencephalographic slow wave activity underestimates the amount of time that the hypothalamus requires to recover from episodes of sleep deprivation. We propose that these hypothalamic changes underlie the well-established relationship between sleep loss and several diseases such as metabolic disorders, stress and depression and that sufficient sleep is vital for autonomic functions controlled by the hypothalamus.

Lesions of the Head Direction Cell System Increase Hippocampal Place Field Repetition.

A central tenet of systems neuroscience is that the mammalian hippocampus provides a cognitive map of the environment. This view is supported by the finding of place cells, neurons whose firing is tuned to specific locations in an animal's environment, within this brain region. Recent work, however, has shown that these cells repeat their firing fields across visually identical maze compartments [1, 2]. This repetition is not observed if these compartments face different directions, suggesting that place cells use a directional input to differentiate otherwise similar local environments [3, 4]. A clear candidate for this input is the head direction cell system. To test this, we disrupted the head direction cell system by lesioning the lateral mammillary nuclei and then recorded place cells as rats explored multiple, connected compartments, oriented in the same or in different directions. As shown previously, we found that place cells in control animals exhibited repeated fields in compartments arranged in parallel, but not in compartments facing different directions. In contrast, the place cells of animals with lesions of the head direction cell system exhibited repeating fields in both conditions. Thus, directional information provided by the head direction cell system appears essential for the angular disambiguation by place cells of visually identical compartments.

Inactivation of the medial mammillary nucleus attenuates theta rhythm activity in the hippocampus in urethane-anesthetized rats.

Although the importance of the mammillary body for memory and learning processes is well known, its exact role has remained vague. The fact, that many neurons in one nucleus of the mammillary body in rats, i.e. the medial mammillary nucleus (MM), fires according with hippocampal theta rhythm, makes this structure crucial for a theta rhythm signaling in so-called extended hippocampal system. These neurons are driven by descending projections from the hippocampal formation, but it is still unknown whether the mammillary body only conveys theta rhythm or may also modulate it. In the present study, we investigated the effect of pharmacological inactivation (local infusion of 0.5µl of 20% procaine hydrochloride solution) of the MM on hippocampal theta rhythm in urethane-anesthetized rats. We found that intra-MM procaine microinjections suppress sensory-elicited theta rhythm in the hippocampus by reduction of its amplitude, but not the frequency. Procaine infusion decreased the EEG signal power of low theta frequency bands, i.e. 3-5Hz, down to 9.2% in 3-4Hz band in comparison to pre-injection conditions. After water infusion (control group) no changes of hippocampal EEG signal power were observed. Our findings showed for the first time that inactivation of the MM leads to a disruption of hippocampal theta rhythm in the rat, which may suggest that the mammillary body can regulate theta rhythm signaling in the extended hippocampal system.

The importance of mammillary body efferents for recency memory: towards a better understanding of diencephalic amnesia.

Despite being historically one of the first brain regions linked to memory loss, there remains controversy over the core features of diencephalic amnesia as well as the critical site for amnesia to occur. The mammillary bodies and thalamus appear to be the primary locus of pathology in the cases of diencephalic amnesia, but the picture is complicated by the lack of patients with circumscribed damage. Impaired temporal memory is a consistent neuropsychological finding in Korsakoff syndrome patients, but again, it is unclear whether this deficit is attributable to pathology within the diencephalon or concomitant frontal lobe dysfunction. To address these issues, we used an animal model of diencephalic amnesia and examined the effect of mammillothalamic tract lesions on tests of recency memory. The mammillothalamic tract lesions severely disrupted recency judgements involving multiple items but left intact both recency and familiarity judgements for single items. Subsequently, we used disconnection procedures to assess whether this deficit reflects the indirect involvement of the prefrontal cortex. Crossed-lesion rats, with unilateral lesions of the mammillothalamic tract and medial prefrontal cortex in contralateral hemispheres, were unimpaired on the same recency tests. These results provide the first evidence for the selective importance of mammillary body efferents for recency memory. Moreover, this contribution to recency memory is independent of the prefrontal cortex. More broadly, these findings identify how specific diencephalic structures are vital for key elements of event memory.

Antidepressant drugs specifically inhibiting noradrenaline reuptake enhance recognition memory in rats.

Patients suffering from major depression often experience memory deficits even after the remission of mood symptoms, and many antidepressant drugs do not affect, or impair, memory in animals and humans. However, some antidepressant drugs, after a single dose, enhance cognition in humans (Harmer et al., 2009). To compare different classes of antidepressant drugs for their potential as memory enhancers, we used a version of the novel object recognition task in which rats spontaneously forget objects 24 hr after their presentation. Antidepressant drugs were injected systemically 30 min before or directly after the training phase (Session 1 [S1]). Post-S1 injections were used to test for specific memory-consolidation effects. The noradrenaline reuptake inhibitors reboxetine and atomoxetine, as well as the serotonin noradrenaline reuptake inhibitor duloxetine, injected prior to S1 significantly enhanced recognition memory. In contrast, the serotonin reuptake inhibitors citalopram and paroxetine and the cyclic antidepressant drugs desipramine and mianserin did not enhance recognition memory. Post-S1 injection of either reboxetine or citalopram significantly enhanced recognition memory, indicating an effect on memory consolidation. The fact that citalopram had an effect only when injected after S1 suggests that it may counteract its own consolidation-enhancing effect by interfering with memory acquisition. However, pretreatment with citalopram did not attenuate reboxetine's memory-enhancing effect. The D1/5-receptor antagonist SCH23390 blunted reboxetine's memory-enhancing effect, indicating a role of dopaminergic transmission in reboxetine-induced recognition memory enhancement. Our results suggest that antidepressant drugs specifically inhibiting noradrenaline reuptake enhance cognition and may be beneficial in the treatment of cognitive symptoms of depression.

Behavioral effects of deep brain stimulation of different areas of the Papez circuit on memory- and anxiety-related functions.

Deep brain stimulation (DBS) has gained interest as a potential therapy for advanced treatment-resistant dementia. However, possible targets for DBS and the optimal stimulation parameters are not yet clear. Here, we compared the effects of DBS of the CA1 sub-region of the hippocampus, mammillothalamic tract, anterior thalamic nucleus, and entorhinal cortex in an experimental rat model of dementia. Rats with scopolamine-induced amnesia were assessed in the object location task with different DBS parameters. Moreover, anxiety-related side effects were evaluated in the elevated zero maze and open field. After sacrifice, we applied c-Fos immunohistochemistry to assess which memory-related regions were affected by DBS. When comparing all structures, DBS of the entorhinal cortex and CA1 sub-region was able to restore memory loss when a specific set of stimulation parameters was used. No anxiety-related side effects were found following DBS. The beneficial behavioral performance of CA1 DBS rats was accompanied with an activation of cells in the anterior cingulate gyrus. Therefore, we conclude that acute CA1 DBS restores memory loss possibly through improved attentional and cognitive processes in the limbic cortex.

Thalamic abnormalities are a cardinal feature of alcohol-related brain dysfunction.

Two brain networks are particularly affected by the harmful effect of chronic and excessive alcohol consumption: the circuit of Papez and the frontocerebellar circuit, in both of which the thalamus plays a key role. Shrinkage of the thalamus is more severe in alcoholics with Korsakoff's syndrome (KS) than in those without neurological complication (AL). In accordance with the gradient effect of thalamic abnormalities between AL and KS, the pattern of brain dysfunction in the Papez's circuit results in anterograde amnesia in KS and only mild-to-moderate episodic memory disorders in AL. On the opposite, dysfunction of the frontocerebellar circuit results in a similar pattern of working memory and executive deficits in the AL and KS. Several hypotheses, mutually compatible, can be drawn to explain that the severe thalamic shrinkage observed in KS has different consequences in the neuropsychological profile associated with the two brain networks.

Lesions of hypothalamic mammillary body desynchronise milk-ejection bursts of rat bilateral supraoptic oxytocin neurones.

Successful milk ejection depends on a bolus release of oxytocin, which results from the synchronised burst firing of magnocellular oxytocin neurones in several hypothalamic nuclei. Despite extensive studies of the mechanism underlying the burst synchrony of oxytocin neurones in the same nucleus, brain regions controlling burst synchronisation among different nuclei remain elusive. We hypothesised that some structures in the ventroposterior hypothalamus may function as the major component of neural circuits controlling burst synchronisation of bilateral oxytocin neurones. To test this hypothesis, we recorded burst firing of bilateral oxytocin neurones in the two supraoptic nuclei after microsurgical disconnection of different hypothalamic regions in anaesthetised lactating rats. The results obtained showed that the interhemispheric section of the caudal part of the hypothalamus but not the rostral hypothalamus resulted in burst desynchronisation. The difference in burst onset time between paired bursts of bilateral oxytocin neurones was 129.2 ± 34.7 s, which is significantly (P < 0.01) longer than that of sham-lesioned controls (0.24 ± 0.02 s). Hypothalamic lesions leading to the desynchronisation involved the mammillary body, supramammillary nucleus and tuberomammillary nucleus in the ventroposterior hypothalamus. Consistently, electrolytic lesion of the median part of this mammillary body region also desynchronised the burst of bilateral oxytocin neurones and disrupted milk ejections. These results indicate that the mammillary body region is critically involved in the burst synchronisation of bilateral oxytocin neurones during suckling and possibly functions as the major component of a putative synchronisation centre.

Acetylcholine facilitates recovery of episodic memory after brain damage.

Episodic memory depends on a network of interconnected brain structures including the inferior temporal cortex, hippocampus, fornix, and mammillary bodies. We have previously shown that a moderate episodic memory impairment in monkeys with transection of the fornix is exacerbated by prior depletion of acetylcholine from inferotemporal cortex, despite the fact that depletion of acetylcholine from inferotemporal cortex on its own has no effect on episodic memory. Here we show that this effect occurs because inferotemporal acetylcholine facilitates recovery of function following structural damage within the neural circuit for episodic memory. Episodic memory impairment caused by lesions of the mammillary bodies, like fornix transection, was exacerbated by prior removal of temporal cortical acetylcholine. However, removing temporal cortical acetylcholine after the lesion of the fornix or mammillary bodies did not increase the severity of the impairment. This lesion order effect suggests that acetylcholine within the inferior temporal cortex ordinarily facilitates functional recovery after structural lesions that impair episodic memory. In the absence of acetylcholine innervation to inferotemporal cortex, this recovery is impaired and the amnesia caused by the structural lesion is more severe. These results suggest that humans with loss of cortical acetylcholine function, for example in Alzheimer's disease, may be less able to adapt to memory impairments caused by structural neuronal damage to areas in the network important for episodic memory.

Extra-hippocampal subcortical limbic involvement predicts episodic recall performance in multiple sclerosis.

BACKGROUND: Episodic memory impairment is a common but poorly-understood phenomenon in multiple sclerosis (MS). We aim to establish the relative contributions of reduced integrity of components of the extended hippocampal-diencephalic system to memory performance in MS patients using quantitative neuroimaging. METHODOLOGY/PRINCIPAL FINDINGS: 34 patients with relapsing-remitting MS and 24 healthy age-matched controls underwent 3 T MRI including diffusion tensor imaging and 3-D T1-weighted volume acquisition. Manual fornix regions-of-interest were used to derive fornix fractional anisotropy (FA). Normalized hippocampal, mammillary body and thalamic volumes were derived by manual segmentation. MS subjects underwent visual recall, verbal recall, verbal recognition and verbal fluency assessment. Significant differences between MS patients and controls were found for fornix FA (0.38 vs. 0.46, means adjusted for age and fornix volume, P<.0005) and mammillary body volumes (age-adjusted means 0.114 ml vs. 0.126 ml, P<.023). Multivariate regression analysis identified fornix FA and mammillary bodies as predictor of visual recall (R(2) = .31, P = .003, P = .006), and thalamic volume as predictive of verbal recall (R(2) = .37, P<.0005). No limbic measures predicted verbal recognition or verbal fluency. CONCLUSIONS/SIGNIFICANCE: These findings indicate that structural and ultrastructural alterations in subcortical limbic components beyond the hippocampus predict performance of episodic recall in MS patients with mild memory dysfunction.

Impairment in material-specific long-term memory following unilateral mediodorsal thalamic damage and presumed partial disconnection of the mammillo-thalamic tract.

Neuropsychological findings suggest material-specific lateralization of the medial temporal lobe's role in long-term memory, with greater left-sided involvement in verbal memory, and greater right-sided involvement in visual memory. Whether material-specific lateralization of long-term memory also extends to the anteromedial thalamus remains uncertain. We report two patients with unilateral right (OG) and left (SM) mediodorsal thalamic pathology plus probable correspondingly lateralized damage of the mammillo-thalamic tract. The lesions were mapped using high-resolution structural magnetic resonance imaging and schematically reconstructed. Mean absolute volume estimates for the mammillary bodies, hippocampus, perirhinal cortex, and ventricles are also presented. Estimates of visual and verbal recall and item recognition memory were obtained using the Doors and People, the Rey Complex Figure Test, and the Logical Memory subtests of the Wechsler Memory Scales. Each patient's performance was compared to a group of healthy volunteers matched for demographic characteristics, premorbid IQ, and current levels of functioning. A striking double dissociation was evident in material-specific long-term memory, with OG showing significant impairments in visual memory but not verbal memory, and SM showing the opposite profile of preserved visual memory and significantly impaired verbal memory. These impairments affected both recall and item recognition. The reported double dissociation provides the strongest evidence yet that material-specific lateralization of long-term memory also extends to the anteromedial thalamus. The findings are also discussed in relation to proposals that distinct anatomical regions within the medial temporal lobe, anteromedial thalamus, and associated tracts make qualitatively different contributions to recall and item recognition.

Unraveling the contributions of the diencephalon to recognition memory: a review.

Both clinical investigations and studies with animals reveal nuclei within the diencephalon that are vital for recognition memory (the judgment of prior occurrence). This review seeks to identify these nuclei and to consider why they might be important for recognition memory. Despite the lack of clinical cases with circumscribed pathology within the diencephalon and apparent species differences, convergent evidence from a variety of sources implicates a subgroup of medial diencephalic nuclei. It is supposed that the key functional interactions of this subgroup of diencephalic nuclei are with the medial temporal lobe, the prefrontal cortex, and with cingulate regions. In addition, some of the clinical evidence most readily supports dual-process models of recognition, which assume two independent cognitive processes (recollective-based and familiarity-based) that combine to direct recognition judgments. From this array of information a "multi-effect multi-nuclei" model is proposed, in which the mammillary bodies and the anterior thalamic nuclei are of preeminent importance for recollective-based recognition. The medial dorsal thalamic nucleus is thought to contribute to familiarity-based recognition, but this nucleus, along with various midline and intralaminar thalamic nuclei, is also assumed to have broader, indirect effects upon both recollective-based and familiarity-based recognition.